The immunopathogenesis of rheumatoid arthritis.
Rheumatoid arthritis is a chronic inflammatory polyarthritis whose etiology remains uncertain. Recently we have learned that autoimmunity to citrullinated protein antigens has specificity for rheumatoid arthritis and defines a clinically and genetically distinct form of the disease. Multiple genes contribute to disease susceptibility, with the HLA locus accounting for 30% to 50% of overall genetic risk. Five risk loci have been identified and validated: HLA-DRB1, PTPN22, STAT4, a region in 6q23, and the TRAF1/C5 locus. Also, there is renewed interest in the contribution of T cells to ongoing inflammation in rheumatoid arthritis. Autoantibodies to citrullinated protein epitopes are specific for rheumatoid arthritis, are associated with a more aggressive disease course, and are pathogenic in an animal model of autoimmune arthritis. There is a strong association between shared-epitope-expressing HLA-DRB1 alleles and the development of rheumatoid arthritis associated with autoimmunity to citrullinated protein antigens.
Imboden
John B
JB
Department of Medicine, University of California, and Division of Rheumatology, San Francisco General Hospital, San Francisco, CA 94110, USA. jimboden@medsfgh.ucsf.edu
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000235:genetics; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D010456:Peptides, Cyclic / Q000276:immunology; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide